Zhishuo Zhang1,2, Wenxia Zhao3,2, Yiming Li3,2, Yang Li3, Hanzeng Cheng4,2, Liyun Zheng3, Xiaoyu Sun2, Hao Liu5, Rongguang Shao6. 1. Department of Organ Transplantation and Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China. 2. School of Pharmacy, Department of Pharmacology, China Medical University, Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Shenyang, Liaoning, China. 3. NHC Key Laboratory of Antibiotic Bioengineering, Laboratory of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Tiantan Xili, Beijing, 100050, China. 4. Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, China. 5. Department of Organ Transplantation and Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China. liuhaodoctor@hotmail.com. 6. NHC Key Laboratory of Antibiotic Bioengineering, Laboratory of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Tiantan Xili, Beijing, 100050, China. rgshao@163.com.
Abstract
BACKGROUND: Ubiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect and biological functional mechanism of YOD1 in pancreatic cancer are still unclear. RESULTS: In the GEO and TCGA databases, YOD1 mRNA expression is significantly up regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P < 0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8 + T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell, Immunohistochemistry (IHC), Western blot and Flow Cytometry indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells and affect the immune microenvironment. CONCLUSION: Our results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.
BACKGROUND: Ubiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect and biological functional mechanism of YOD1 in pancreatic cancer are still unclear. RESULTS: In the GEO and TCGA databases, YOD1 mRNA expression is significantly up regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P < 0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8 + T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell, Immunohistochemistry (IHC), Western blot and Flow Cytometry indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells and affect the immune microenvironment. CONCLUSION: Our results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.
Authors: Long Zhang; FangFang Zhou; Yvette Drabsch; Rui Gao; B Ewa Snaar-Jagalska; Craig Mickanin; Huizhe Huang; Kelly-Ann Sheppard; Jeff A Porter; Chris X Lu; Peter ten Dijke Journal: Nat Cell Biol Date: 2012-06-17 Impact factor: 28.824
Authors: Vésteinn Thorsson; David L Gibbs; Scott D Brown; Denise Wolf; Dante S Bortone; Tai-Hsien Ou Yang; Eduard Porta-Pardo; Galen F Gao; Christopher L Plaisier; James A Eddy; Elad Ziv; Aedin C Culhane; Evan O Paull; I K Ashok Sivakumar; Andrew J Gentles; Raunaq Malhotra; Farshad Farshidfar; Antonio Colaprico; Joel S Parker; Lisle E Mose; Nam Sy Vo; Jianfang Liu; Yuexin Liu; Janet Rader; Varsha Dhankani; Sheila M Reynolds; Reanne Bowlby; Andrea Califano; Andrew D Cherniack; Dimitris Anastassiou; Davide Bedognetti; Younes Mokrab; Aaron M Newman; Arvind Rao; Ken Chen; Alexander Krasnitz; Hai Hu; Tathiane M Malta; Houtan Noushmehr; Chandra Sekhar Pedamallu; Susan Bullman; Akinyemi I Ojesina; Andrew Lamb; Wanding Zhou; Hui Shen; Toni K Choueiri; John N Weinstein; Justin Guinney; Joel Saltz; Robert A Holt; Charles S Rabkin; Alexander J Lazar; Jonathan S Serody; Elizabeth G Demicco; Mary L Disis; Benjamin G Vincent; Ilya Shmulevich Journal: Immunity Date: 2018-04-05 Impact factor: 43.474